Social cognition in Parkinson's disease and functional movement disorders.

INTRODUCTION: Functional movement disorders (FMD) can overlap with Parkinson's disease (PD), and distinguishing between the two clinical conditions can be complex. Framing social cognition (theory of mind) (TOM) disorder, attention deficit, and psychodynamic features of FMD and PD may improve diagnosis. METHODS: Subjects with FMD and PD and healthy controls (HC) were administered tasks assessing TOM abilities and attention. The psychodynamic hypothesis of conversion disorder was explored by a questionnaire assessing dissociative symptoms. A comprehensive battery of neuropsychological tasks was also administered to FMD and PD. RESULTS: Although both FMD and PD scored lower than HC on all TOM tests, significant correlations between TOM and neuropsychological tasks were found only in PD but not in FMD. Only PD showed a reduction in attentional control. Dissociative symptoms occurred only in FMD. DISCUSSION: Cognitive-affective disturbances are real in FMD, whereas they are largely dependent on cognitive impairment in PD. Attentional control is preserved in FMD compared to PD, consistent with the hypothesis that overload of voluntary attentional orientation may be at the basis of the onset of functional motor symptoms. On a psychodynamic level, the confirmation of dissociative symptoms in FMD supports the conversion disorder hypothesis. CONCLUSION: FMD and PD can be distinguished on an affective and cognitive level. At the same time, however, the objective difficulty often encountered in distinguishing between the two pathologies draws attention to how blurred the boundary between 'organic' and 'functional' can be.

Chronic Pharmacological Increase of Neuronal Activity Improves Sensory-Motor Dysfunction in Spinal Muscular Atrophy Mice.

Dysfunction of neuronal circuits is an important determinant of neurodegenerative diseases. Synaptic dysfunction, death, and intrinsic activity of neurons are thought to contribute to the demise of normal behavior in the disease state. However, the interplay between these major pathogenic events during disease progression is poorly understood. Spinal muscular atrophy (SMA) is a neurodegenerative disease caused by a deficiency in the ubiquitously expressed protein SMN and is characterized by motor neuron death, skeletal muscle atrophy, as well as dysfunction and loss of both central and peripheral excitatory synapses. These disease hallmarks result in an overall reduction of neuronal activity in the spinal sensory-motor circuit. Here, we show that increasing neuronal activity by chronic treatment with the FDA-approved potassium channel blocker 4-aminopyridine (4-AP) improves motor behavior in both sexes of a severe mouse model of SMA. 4-AP restores neurotransmission and number of proprioceptive synapses and neuromuscular junctions (NMJs), while having no effects on motor neuron death. In addition, 4-AP treatment with pharmacological inhibition of p53-dependent motor neuron death results in additive effects, leading to full correction of sensory-motor circuit pathology and enhanced phenotypic benefit in SMA mice. Our in vivo study reveals that 4-AP-induced increase of neuronal activity restores synaptic connectivity and function in the sensory-motor circuit to improve the SMA motor phenotype.SIGNIFICANCE STATEMENT Spinal muscular atrophy (SMA) is a neurodegenerative disease, characterized by synaptic loss, motor neuron death, and reduced neuronal activity in spinal sensory-motor circuits. However, whether these are parallel or dependent events is unclear. We show here that long-term increase of neuronal activity by the FDA-approved drug 4-aminopyridine (4-AP) rescues the number and function of central and peripheral synapses in a SMA mouse model, resulting in an improvement of the sensory-motor circuit and motor behavior. Combinatorial treatment of pharmacological inhibition of p53, which is responsible for motor neuron death and 4-AP, results in additive beneficial effects on the sensory-motor circuit in SMA. Thus, neuronal activity restores synaptic connections and improves significantly the severe SMA phenotype.

Relation Between the Corticospinal Tract State and Activities of Daily Living in Patients With Intracerebral Hemorrhage.

BACKGROUND AND PURPOSE: We investigated the relation between the ipsilesional corticospinal tract (CST) state and activity of daily living independence in patients with chronic intracerebral hemorrhage. METHODS: Fifty-six consecutive patients with unilateral intracerebral hemorrhage and 38 healthy control subjects were recruited for this study. The Motricity index and the modified Barthel index were used to evaluate motor function of the affected extremities and activity of daily living independence, respectively. The diffusion tensor imaging parameter values for fractional anisotropy (FA) and voxel number (VN) of the CST were determined. Ratios of the ipsilesional to the contralesional CST measures were calculated and are presented as the CST-ratio (FA value and VN). RESULTS: The FA value and VN of the ipsilesional CST and the CST-ratio in the patient group were lower than those of the control group (P<0.05). There was a strong positive correlation between the Motricity index score of the affected extremities and the modified Barthel index score (P<0.05), while the FA value and VN of the ipsilesional CST and the CST-ratio showed moderate and strong positive correlations with the Motricity index and modified Barthel index scores, respectively (P<0.05). In addition, the VN of the ipsilesional CST showed excellent utility as a classifier, whereas the FA value of the ipsilesional CST and the FA value and VN of the CST-ratio showed good classifier utility (P<0.05). CONCLUSIONS: We demonstrated that impairment of activity of daily living independency was closely related to the injury severity of the ipsilesional CST in patients with chronic intracerebral hemorrhage. In addition, the injury severity of the ipsilesional CST can be used to classify the degree of activity of daily living independency. Registration: URL: http://www.e-irb.com/index.jsp; Unique identifier: 2021-03-014.

DNAJB6 suppresses alpha-synuclein induced pathology in an animal model of Parkinson's disease.

BACKGROUND: α-synuclein (α-syn) aggregation can lead to degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc) as invariably observed in patients with Parkinson's Disease (PD). The co-chaperone DNAJB6 has previously been found to be expressed at higher levels in PD patients than in control subjects and was also found in Lewy bodies. Our previous experiments showed that knock out of DNAJB6 induced α-syn aggregation in cellular level. However, effects of overexpression of DNAJB6 against α-syn aggregation remains to be investigated. METHODS: We used a α-syn CFP/YFP HEK293 FRET cell line to investigate the effects of overexpression of DNAJB6 in cellular level. α-syn aggregation was induced by transfection α-syn preformed fibrils (PPF), then was measured FRET analysis. We proceeded to investigate if DNAJB6b can impair α-syn aggregation and toxicity in an animal model and used adeno associated vira (AAV6) designed to overexpress of human wt α-syn, GFP-DNAJB6 or GFP in rats. These vectors were injected into the SNpc of the rats, unilaterally. Rats injected with vira to express α-syn along with GFP in the SNpc where compared to rats expressing α-syn and GFP-DNAJB6. We evaluated motor functions, dopaminergic cell death, and axonal degeneration in striatum. RESULTS: We show that DNAJB6 prevent α-syn aggregation induced by α-syn PFF's, in a cell culture model. In addition, we observed α-syn overexpression caused dopaminergic cell death and that this was strongly reduced by co-expression of DNAJB6b. The lesion caused by α-syn overexpression resulted in behavior deficits, which increased over time as seen in stepping test, which was rescued by co-expression of DNAJB6b. CONCLUSION: We here demonstrate for the first time that DNAJB6 is a strong suppressor of α-syn aggregation in cells and in animals and that this results in a suppression of dopaminergic cell death and PD related motor deficits in an animal model of PD.

Inhibition of TLR4 signaling protects mice from sensory and motor dysfunction in an animal model of autoimmune peripheral neuropathy.

BACKGROUND: While the etiology remains elusive, macrophages and T cells in peripheral nerves are considered as effector cells mediating autoimmune peripheral neuropathy (APN), such as Guillain-Barre syndrome. By recognizing both pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs) signals, TLRs play a central role in the initiation of both innate and adaptive immune responses. In this study, we aimed to understand the involvement of TLR4 in the pathogenesis of APN and explore the potential of TLR4 as a drug target for therapeutic use. METHODS: APN was induced by a partial ligation on one of the sciatic nerves in B7.2 (L31) transgenic mice which possess a predisposed inflammatory background. APN pathology and neurological function were evaluated on the other non-injured sciatic nerve. RESULTS: TLR4 and its endogenous ligand HMGB1 were highly expressed in L31 mice, in circulating immune cells and in peripheral nerves. Enhanced TLR4 signaling was blocked with TAK 242, a selective TLR4 inhibitor, before and after disease onset. Intraperitoneal administration of TAK 242 not only inhibited monocyte, macrophage and CD8+ T cell activation, but also reduced the release of pro-inflammatory cytokines. TAK 242 protected mice from severe myelin and axonal loss, resulting in a remarkable improvement in mouse motor and sensory functions. TAK 242 was effective in alleviating the disease in both preventive and reversal paradigms. CONCLUSION: The study identified the critical contribution of TLR4-mediated macrophage activation in disease course and provided strong evidence to support TLR4 as a useful drug target for treating inflammatory autoimmune neuropathy.

Variants in the SK2 channel gene (KCNN2) lead to dominant neurodevelopmental movement disorders.

KCNN2 encodes the small conductance calcium-activated potassium channel 2 (SK2). Rodent models with spontaneous Kcnn2 mutations show abnormal gait and locomotor activity, tremor and memory deficits, but human disorders related to KCNN2 variants are largely unknown. Using exome sequencing, we identified a de novo KCNN2 frameshift deletion in a patient with learning disabilities, cerebellar ataxia and white matter abnormalities on brain MRI. This discovery prompted us to collect data from nine additional patients with de novo KCNN2 variants (one nonsense, one splice site, six missense variants and one in-frame deletion) and one family with a missense variant inherited from the affected mother. We investigated the functional impact of six selected variants on SK2 channel function using the patch-clamp technique. All variants tested but one, which was reclassified to uncertain significance, led to a loss-of-function of SK2 channels. Patients with KCNN2 variants had motor and language developmental delay, intellectual disability often associated with early-onset movement disorders comprising cerebellar ataxia and/or extrapyramidal symptoms. Altogether, our findings provide evidence that heterozygous variants, likely causing a haploinsufficiency of the KCNN2 gene, lead to novel autosomal dominant neurodevelopmental movement disorders mirroring phenotypes previously described in rodents.

Psychosis and longitudinal outcomes in Huntington disease: the COHORT Study.

OBJECTIVE: Huntington disease (HD) is an autosomal dominant neurodegenerative disease involving motor disturbances, cognitive decline and psychiatric symptoms. Psychotic symptoms occur in a significant proportion of patients. We sought to characterise the clinical outcomes of this group of patients. METHODS: Data were drawn from the Cooperative Huntington Observational Research Trial, a prospective, multi-centre observational study. 1082 patients with HD were recruited. Measures of cognition, function, behavioural disturbance and motor function were completed annually over 5 years. RESULTS: Overall, 190 patients (17.6%) displayed psychotic symptoms. These patients demonstrated worse cognition, function and behavioural disturbances than patients without psychosis over time. Patients with psychosis also demonstrated lower levels of chorea than patients without psychosis, despite adjusting for concurrent antipsychotic and tetrabenazine use. CONCLUSIONS: Psychosis in HD is associated with poorer outcomes in cognition, function and behavioural symptoms. Patients with psychotic symptoms may also have less chorea. Altogether, the findings suggest patients with psychosis have a distinct clinical course.

Internal Versus External Frame of Reference in Functional Movement Disorders.

OBJECTIVE: The purpose of this study was to determine whether patients with functional movement disorders (FMDs) differ in their internal versus external locus of control (LOC) and whether LOC in these patients affected disease severity, quality of life, and functional impairment compared with control subjects with degenerative (Parkinson's disease) and nondegenerative (focal dystonia) neurological conditions. METHODS: A total of 156 patients with FMD (N=45), Parkinson's disease (N=64), and focal dystonia (N=47) were recruited between June 2015 and August 2017. The authors administered the general Levenson Multidimensional LOC (LOC-G) and health-specific Multidimensional Health LOC (LOC-H) scales. An internal LOC was represented similarly in both scales: the external LOC included "chance" and "powerful others" in the LOC-G measure and chance, "other people," and "doctors" in the LOC-H measure. Quality of life, functional impairment, and FMD severity were assessed. One-way analysis of variance and adjusted logistic regressions were used, as well as ordinary least-squares between and within groups, respectively. RESULTS: Patients with FMD had lower external chance LOC-G scores compared with patients in the Parkinson's disease group (odds ratio=0.90, p=0.03) and higher internal (odds ratio=1.22, p=0.01) and lower external (odds ratio=0.77, p=0.02) doctors LOC-H scores compared with patients in the focal dystonia group. External powerful others LOC-G score was associated with functional impairment (regression coefficient=-0.04, p=0.02). There were no effects of LOC on quality of life or disease severity. CONCLUSIONS: Patients with FMD exhibited high "within our control" internal general and health-specific frame of reference. LOC had no influence on quality of life or disease severity in this patient population.

Nonepileptic attack disorder and functional movement disorder: A clinical continuum?

Nonepileptic attack disorder (NEAD) and functional movement disorder (FMD) are functional neurological disorders commonly seen in neuropsychiatry services. Although their initial referral pathways involve epileptologists (NEAD) and specialists in movement disorders (FMD), these conditions are currently classified as two possible manifestations of a single underlying conversion disorder. We set out to compare the characteristics of patients with NEAD and patients with FMD in order to quantify the degree of overlap between these patient groups. We retrospectively reviewed comprehensive clinical data from 146 consecutive patients with functional neurological disorders (NEAD: n = 117; FMD: n = 29) attending a specialist Neuropsychiatry Clinic run by a single Consultant in Behavioral Neurology. The two clinical groups were directly compared with regard to demographic and clinical characteristics, as well as somatic and psychiatric presentations. The results showed that in most features, there were no significant differences between patients with NEAD and patients with FMD. However, patients with NEAD reported an earlier age at onset (p = 0.033) and a higher proportion of acute onset (p = 0.037), alterations of consciousness (p = 0.001), and headache (p = 0.042), whereas patients with FMD reported a higher prevalence of childhood abuse (p = 0.008), as well as mobility problems (p = 0.007) and comorbid functional symptoms (dysarthria, p = 0.004; dizziness, p = 0.035; weakness, p = 0.049). Despite different phenotypic presentations, NEAD and FMD might represent a clinical continuum, with relevant implications in terms of both diagnostic strategies and treatment approaches.

[Advanced Parkinson's disease characteristics in clinical practice: Results from the OBSERVE-PD study and sub-analysis of the Hungarian data]. / Az elôrehaladott Parkinson-kór jellemzôi a klinikai gyakorlatban: az OBSERVE-PD vizsgálat eredményei és a magyarországi alcsoport elemzése.

BACKGROUND AND PURPOSE: The majority of patients with advanced Parkinson's disease are treated at specialized movement disorder centers. Currently, there is no clear consensus on how to define the stages of Parkinson's disease; the proportion of Parkinson's patients with advanced Parkinson's disease, the referral process, and the clinical features used to characterize advanced Parkinson's disease are not well delineated. The primary objective of this observational study was to evaluate the proportion of Parkinson's patients identified as advanced patients according to physician's judgment in all participating movement disorder centers across the study. Here we evaluate the Hungarian subset of the participating patients. METHODS: The study was conducted in a cross-sectional, non-interventional, multi-country, multi-center format in 18 countries. Data were collected during a single patient visit. Current Parkinson's disease status was assessed with Unified Parkinson's Disease Rating Scale (UPDRS) parts II, III, IV, and V (modified Hoehn and Yahr staging). Non-motor symptoms were assessed using the PD Non-motor Symptoms Scale (NMSS); quality of life was assessed with the PD 8-item Quality-of-Life Questionnaire (PDQ-8). Parkinson's disease was classified as advanced versus non-advanced based on physician assessment and on questions developed by the Delphi method. RESULTS: Overall, 2627 patients with Parkinson's disease from 126 sites were documented. In Hungary, 100 patients with Parkinson's disease were documented in four movement disorder centers, and, according to the physician assessment, 50% of these patients had advanced Parkinson's disease. Their mean scores showed significantly higher impairment in those with, versus without advanced Parkinson's disease: UPDRS II (14.1 vs. 9.2), UPDRS IV Q32 (1.1 vs. 0.0) and Q39 (1.1 vs. 0.5), UPDRS V (2.8 vs. 2.0) and PDQ-8 (29.1 vs. 18.9). CONCLUSION: Physicians in Hungarian movement disorder centers assessed that half of the Parkinson's patients had advanced disease, with worse motor and non-motor symptom severity and worse QoL than those without advanced Parkinson's disease. Despite being classified as eligible for invasive/device-aided treatment, that treatment had not been initiated in 25% of these patients.

The spectrum of involuntary vocalizations in humans: A video atlas.

In clinical practice, involuntary vocalizing behaviors are typically associated with Tourette syndrome and other tic disorders. However, they may also be encountered throughout the entire tenor of neuropsychiatry, movement disorders, and neurodevelopmental syndromes. Importantly, involuntary vocalizing behaviors may often constitute a predominant clinical sign, and, therefore, their early recognition and appropriate classification are necessary to guide diagnosis and treatment. Clinical literature and video-documented cases on the topic are surprisingly scarce. Here, we pooled data from 5 expert centers of movement disorders, with instructive video material to cover the entire range of involuntary vocalizations in humans. Medical literature was also reviewed to document the range of possible etiologies associated with the different types of vocalizing behaviors and to explore treatment options. We propose a phenomenological classification of involuntary vocalizations within different categorical domains, including (1) tics and tic-like vocalizations, (2) vocalizations as part of stereotypies, (3) vocalizations as part of dystonia or chorea, (4) continuous vocalizing behaviors such as groaning or grunting, (5) pathological laughter and crying, (6) vocalizations resembling physiological reflexes, and (7) other vocalizations, for example, those associated with exaggerated startle responses, as part of epilepsy and sleep-related phenomena. We provide comprehensive lists of their associated etiologies, including neurodevelopmental, neurodegenerative, neuroimmunological, and structural causes and clinical clues. We then expand on the pathophysiology of the different vocalizing behaviors and comment on available treatment options. Finally, we present an algorithmic approach that covers the wide range of involuntary vocalizations in humans, with the ultimate goal of improving diagnostic accuracy and guiding appropriate treatment. © 2019 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

Motoric cognitive risk syndrome and mortality: results from the EPIDOS cohort.

BACKGROUND AND PURPOSE: Cognitive impairment, slow walking speed and motoric cognitive risk syndrome (MCR) have separately been associated with an increased risk for mortality in the short term. The aim of the study was to examine the association of MCR and its components [i.e. subjective cognitive complaint (SCC) and slow walking speed] with short-, medium- and long-term mortality in older community-dwellers. METHODS: In all, 3778 participants from the Epidémiologie de l'Ostéoporose (EPIDOS) study were selected. MCR was defined as the combination of slow walking speed and SCC in participants without major neurocognitive disorders. Deaths were prospectively recorded using mail, phone calls, questionnaires and/or the French national death registry at 5, 10, 15 and 19 (end of follow-up period) years. RESULTS: Over the follow-up of 19 years, 80.5% (n = 3043) participants died. Slow walking speed and MCR were associated with mortality [hazard ratio (HR) 1.20 with P = 0.004 for slow walking speed and HR = 1.26 with P = 0.002 for MCR at 10 years; HR = 1.27 with P ≤ 0.001 for slow walking speed and HR = 1.22 with P = 0.001 for MCR at 15 years; HR = 1.41 with P ≤ 0.001 at 19 years for slow walking speed and MCR]. There was no association between SCC and mortality. Kaplan-Meier distributions of mortality showed that participants with MCR and slow walking speed died earlier compared to healthy participants and those with SCC (P < 0.001). CONCLUSIONS: Slow walking speed and MCR were associated with an increased risk for mortality at the medium and long term, whereas no association was found with SCC.

Hiding in Plain Sight: Functional Neurological Disorders in the News.

OBJECTIVE: Functional movement and seizure disorders are still widely misunderstood and receive little public and academic attention. This is in stark contrast to their high prevalence and levels of associated disability. In an exploratory observational study, the authors examined whether the relative lack of media coverage of functional neurological disorders is in part due to misidentification in "human interest" news stories. METHODS: Thirteen recent news stories from high-impact English-language media outlets that portrayed patients with complex symptoms either attributed to other diagnoses or presented as medical mysteries were identified using online keyword searches. All selected news stories contained video or still images displaying relevant symptoms. Cases were categorized into movement disorders or seizure disorders and were then independently assessed by 10 respective expert raters. For each category, one story of a patient whose symptoms were due to a well-recognized neurological disease was also included. Both the diagnostic category and the respective confidence level were reported by each rater for each case. The interrater agreement was calculated for each group of disorders. RESULTS: The raters confirmed almost unanimously that all presented news stories except the negative control cases portrayed misidentified functional movement or seizure disorders. The interrater agreement and average diagnostic confidence were high. CONCLUSIONS: Functional neurological disorders are often wrongly considered a rare medical curiosity of the past. However, these findings suggest that, while they are largely absent from public discourse, they often appear in the news incognito, hiding in plain sight.

Loss of TrkB Signaling in Parvalbumin-Expressing Basket Cells Results in Network Activity Disruption and Abnormal Behavior.

The GABAergic system is regulated by the brain-derived neurotrophic factor (BDNF)/Tropomyosin-related kinase B (TrkB) pathway, but the cell-intrinsic role of TrkB signaling in parvalbumin cortical interneuron development and function is unclear. We performed conditional ablation of the TrkB receptor in parvalbumin-expressing (PV) interneurons to study whether postnatal loss of TrkB in parvalbumin cells affects their survival, connectivity, spontaneous and evoked neuronal activity and behavior. Using in vivo recordings of local field potentials, we found reduced gamma oscillations in the sensory cortex of PVcre+; TrkBF/F conditional knockout mice (TrkB cKO), along with increased firing of putative excitatory neurons. There was a significant downregulation in parvalbumin neuron number in cerebral and cerebellar cortices of TrkB cKO mice. In addition, inhibitory synaptic connections between basket cells and pyramidal neurons were profoundly reduced in the neocortex of TrkB cKO mice and there was a loss of cortical volume. TrkB cKO mice also showed profound hyperactivity, stereotypies, motor deficits and learning/memory defects. Our findings demonstrate that the targeting and/or synapse formation of PV-expressing basket cells with principal excitatory neurons require TrkB signaling in parvalbumin cells. Disruption of this signaling has major consequences for parvalbumin interneuron connectivity, network dynamics, cognitive and motor behavior.

Patient Experience with Rechargeable Implantable Pulse Generator Deep Brain Stimulation for Movement Disorders.

BACKGROUND/AIMS: Nonrechargeable deep brain stimulation implantable pulse generators (IPGs) for movement disorders require surgical replacement every few years due to battery depletion. Rechargeable IPGs reduce frequency of replacement surgeries and inherent risks of complications but require frequent recharging. Here, we evaluate patient experience with rechargeable IPGs and define predictive characteristics for higher satisfaction. METHODS: We contacted all patients implanted with rechargeable IPGs at a single center in a survey-based study. We analyzed patient satisfaction with respect to age, diagnosis, target, charging duration, and body mass index. We tabulated hardware-related adverse events. RESULTS: Dystonia patients had significantly higher satisfaction than Parkinson's disease patients in recharging, display, programmer, and training domains. Common positive responses were "fewer surgeries" and "small size." Common negative responses were "difficulty finding the right position to recharge" and "need to recharge every day." Hardware-related adverse events occurred in 21 of 59 participants. CONCLUSION: Patient experience with rechargeable IPGs was largely positive; however, frustrations with recharging and adverse events were common. Dystonia diagnosis was most predictive of high satisfaction across multiple categories, potentially related to expected long disease duration with need for numerous IPG replacements.

Vision does not always help stroke survivors compensate for impaired limb position sense.

BACKGROUND: Position sense is commonly impaired after stroke. Traditional rehabilitation methods instruct patients to visualize their limbs to compensate for impaired position sense. OBJECTIVE: Our goal was to evaluate how the use of vision influences impaired position sense. METHODS: We examined 177 stroke survivors, an average of 12.7 days (+/- 10 days (SD)) post-stroke, and 133 neurologically-intact controls with a robotic assessment of position sense. The robot positioned one limb (affected) and subjects attempted to mirror-match the position using the opposite limb (unaffected). Subjects completed the test without, then with vision of their limbs. We examined three measures of position sense: variability (Var), contraction/expansion (C/E) and systematic shift (Shift). We classified stroke survivors as having full compensation if they performed the robotic task abnormally without vision but corrected performance within the range of normal with vision. Stroke survivors were deemed to have partial compensation if they performed the task outside the range of normal without and with vision, but improved significantly with vision. Those with absent compensation performed the task abnormally in both conditions and did not improve with vision. RESULTS: Many stroke survivors demonstrated impaired position sense with vision occluded [Var: 116 (66%), C/E: 91 (51%), Shift: 52 (29%)]. Of those stroke survivors with impaired position sense, some exhibited full compensation with vision [Var: 23 (20%), C/E: 42 (46%), Shift: 32 (62%)], others showed partial compensation [Var: 37 (32%), C/E: 8 (9%), Shift: 3 (6%)] and many displayed absent compensation (Var: 56 (48%), C/E: 41 (45%), Shift: 17 (33%)]. Stroke survivors with an affected left arm, visuospatial neglect and/or visual field defects were less likely to compensate for impaired position sense using vision. CONCLUSIONS: Our results indicate that vision does not help many stroke survivors compensate for impaired position sense, at least within the current paradigm. This contrasts with historical reports that vision helps compensate for proprioceptive loss following neurologic injuries.

Malingering and factitious disorder.

Although exaggeration or amplification of symptoms is common in all illness, deliberate deception is rare. In settings associated with litigation/disability evaluation, the rate of malingering may be as high as 30%, but its frequency in clinical practice is not known. We describe the main characteristics of deliberate deception (factitious disorders and malingering) and ways that neurologists might detect symptom exaggeration. The key to establishing that the extent or severity of reported symptoms does not truly represent their severity is to elicit inconsistencies in different domains, but it is not possible to determine whether the reports are intentionally inaccurate. Neurological disorders where difficulty in determining the degree of willed exaggeration is most likely include functional weakness and movement disorders, post-concussional syndrome (or mild traumatic brain injury), psychogenic non-epileptic attacks and complex regional pain syndrome type 1 (especially when there is an associated functional movement disorder). Symptom amplification or even fabrication are more likely if the patient might gain benefit of some sort, not necessarily financial. Techniques to detect deception in medicolegal settings include covert surveillance and review of social media accounts. We also briefly describe specialised psychological tests designed to elicit effort from the patient.

Alpha-synuclein delays mitophagy and targeting Miro rescues neuron loss in Parkinson's models.

Alpha-synuclein is a component of Lewy bodies, the pathological hallmark of Parkinson's disease (PD), and is also mutated in familial PD. Here, by extensively analyzing PD patient brains and neurons, and fly models, we show that alpha-synuclein accumulation results in upregulation of Miro protein levels. Miro is a motor/adaptor on the outer mitochondrial membrane that mediates mitochondrial motility, and is removed from damaged mitochondria to facilitate mitochondrial clearance via mitophagy. PD patient neurons abnormally accumulate Miro on the mitochondrial surface leading to delayed mitophagy. Partial reduction of Miro rescues mitophagy phenotypes and neurodegeneration in human neurons and flies. Upregulation of Miro by alpha-synuclein requires an interaction via the N-terminus of alpha-synuclein. Our results highlight the importance of mitochondria-associated alpha-synuclein in human disease, and present Miro as a novel therapeutic target.

Motor Impairments Correlate with Social Deficits and Restricted Neuronal Loss in an Environmental Model of Autism.

Background: Motor impairments are amongst the earliest and most consistent signs of autism spectrum disorders but are not used as diagnostic criteria. In addition, the relationship between motor and cognitive impairments and their respective neural substrates remain unknown. Methods: Here, we aimed at determining whether a well-acknowledged animal model of autism spectrum disorders, the valproic acid model, displays motor impairments and whether they may correlate with social deficits and neuronal loss within motor brain areas. For this, pregnant female mice (C57BL/6J) received valproic acid (450 mg/kg) at embryonic day 12.5 and offspring underwent a battery of behavioral analyses before being killed for histological correlates in motor cortex, nigrostriatal pathway, and cerebellum. Results: We show that while valproic acid male mice show both social and motor impairments, female mice only show motor impairments. Prenatal valproic acid exposure induces specific cell loss within the motor cortex and cerebellum and that is of higher magnitude in males than in females. Finally, we demonstrate that motor dysfunction correlates with reduced social behavior and that motor and social deficits both correlate with a loss of Purkinje cells within the Crus I cerebellar area. Conclusions: Our results suggest that motor dysfunction could contribute to social and communication deficits in autism spectrum disorders and that motor and social deficits may share common neuronal substrates in the cerebellum. A systematic assessment of motor function in autism spectrum disorders may potentially help the quantitative diagnosis of autism spectrum disorders and strategies aimed at improving motor behavior may provide a global therapeutic benefit.

Incidence and Risk Factors of Kinesiophobia After Total Knee Arthroplasty in Zhengzhou, China: A Cross-Sectional Study.

BACKGROUND: The incidence of and risk factors for kinesiophobia after total knee arthroplasty (TKA) have not been well characterized in the literature. Thus, the aim of this study was to investigate the incidence of postoperative kinesiophobia among patients undergoing TKA and to identify the associated risk factors. METHODS: The simplified Chinese version of the Tampa Scale for Kinesiophobia, Knee Self-Efficacy Scale, Numerical Rating Scale, Simplified Coping Style Questionnaire, and Social Support Rating Scale were used to measure kinesiophobia, self-efficacy, pain intensity, coping styles and social support, respectively. Multivariate logistic regression analyses were utilized to identify the risk factors for postoperative kinesiophobia among TKAs. RESULTS: A total of 862 participants were included in this study. Among all participants, 210 (24.4%) were identified as having kinesiophobia according the Tampa Scale for Kinesiophobia (TSK>37), with a mean score of 32.5 (standard deviation 13.1). A multivariate regression analysis showed that older age (odds ratio [OR] = 2.8, confidence interval [CI] = 2.0-3.7), lower education level (OR = 1.7, CI = 1.3-2.4), negative coping styles (OR = 1.6, CI = 1.0-2.2), less social support (OR = 3.5, CI = 3.1-4.1), lower self-efficacy (OR = 1.4, CI = 1.1-1.7), and greater pain intensity (OR = 2.8, CI = 1.5-5.3) are independent risk factors for kinesiophobia. CONCLUSION: A 24.4% incidence rate of postoperative kinesiophobia was noted in patients following TKA. Older age (most notably ≥76 years old), lower education levels, negative coping styles, greater pain intensity, lower self-efficacy, and less social support were associated with odds of developing postoperative kinesiophobia.